This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To improve in vitro assays to predict the types of antibody responses that will provide optimal benefit against HIV exposure. The overarching hypotheses that we wish to test is that antibody effector function is critical to protection against HIV challenge, that we can dissect the crucial functions important in vivo and that we can use this knowledge to improve in vitro assays to predict the types of antibody responses that will provide optimal benefit against HIV exposure. This project includes two main experiments: In the current studies we use the recombinant Simian Human Immunodeficiency Virus (SHIV) infected-Rhesus macaque model to understand the role of two different functions of the protective antibodies against HIV infection in humans. In the first study we will determine the role of the protective antibodies in killing and eliminating the infected cells. We will treat two groups of animals with two different, but closely related antibodies that were genetically engineered to perform either the killing or the eliminating function well. We will compare the control of viremia in these two groups of animals and between three other groups of animals. One of the latter three groups of animals will not be treated with any antibody, the other group will be treated with an antibody that has both functions, and the third group will be treated with an antibody that has protective activity, but lacks killing activity and does not facilitate the eliminating of the infected cells either. In a second set of experiments we ask whether the protection against SHIV infection is better if one of the two above mentioned functions of the protective antibodies is enhanced. To address this issue we will treat two groups of animals with two different, but closely related antibodies that were genetically engineered to perform just one of these two functions at an enhanced level. We will compare the control of viremia in the two groups of animals and between groups of animals that will not be treated with any antibody, or will be treated with an antibody that has both functions at a normal level. Subproject Progress, Experiment 1: We have selected animals that will participate in the first experiment. We plan to start the studies in March of 2010. This project uses WNPRC Research Services and Animal Services.